Traumatic spinal cord injury is a devastating disease associated with severe sequelae. Despite recent progress in promoting the regeneration of many classes of central nervous system axons after spinal cord injury (SCI), the corticospinal projection remains largely refractory to regeneration. Using a combination of sophisticated experimental approaches in murine models of SCI, the authors demonstrated robust corticospinal axon regeneration, functional synapse formation, and improved skilled forelimb function after grafting multipotent neural progenitor cells into sites of SCI. Corticospinal regeneration requires grafts to be driven toward caudalized (spinal cord), rather than rostralized, fates. Corticospinal axons can also emerge from neural grafts and regenerate beyond the lesion, a process that is potentially related to the attenuation of the glial scar. These findings will be essential for advancing corticospinal regeneration in future translational efforts.

Aspirin is recommended for secondary prevention after transient ischemic attack (TIA) or ischemic stroke on the basis of trials showing a 13% reduction in long-term risk of recurrent stroke, but short-term effects may have been underestimated. In this time-course analysis of aspirin effects after TIA, 15,778 participants from 12 trials of aspirin versus control in secondary prevention were pooled. The severity of early recurrent strokes between treatment groups was analyzed with shift analysis of the modified Rankin Scale score. Aspirin reduced the 6-week risk of recurrent ischemic stroke by about 60% (84 of 8,452 participants in the aspirin group had an ischemic stroke vs. 175 of 7326; hazard ratio 0.42; 95% CI, 0.32 to 0.55; P < 0.0001) and disabling or fatal ischemic stroke by about 70% (36 of 8452 vs. 110 of 7326; hazard ratio 0.29; 95% CI, 0.20 to 0.42; P < 0.0001), with greatest benefit noted in patients presenting with TIA or minor stroke. The effect of aspirin on early recurrent ischemic stroke was due partly to a substantial reduction in severity of the primary event.

Take home message: Medical treatment substantially reduces the risk of early recurrent stroke after transient ischemic attack and minor stroke and aspirin is identified as the key intervention.

The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in urologic oncology. In this prospective randomized controlled trial, the authors aimed at comparing urinary function (urinary domain of the Expanded Prostate Cancer Index Composite [EPIC]) and sexual function (sexual domain of EPIC and International Index of Erectile Function Questionnaire) at 6 weeks, 12 weeks, and 24 months, and oncological outcome (positive surgical margin status and biochemical and imaging evidence of progression at 24 months) in men undergoing either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy. Early outcomes at 6 weeks and 12 weeks were reported in 326 patients. The two techniques yield similar functional outcomes at 12 weeks; examination of the longer-term follow-up data in this trial will help guide future patient and practitioner decisions.

Take home message: In this randomized controlled trial, robotic versus conventional laparoscopic prostatectomy did not reveal significant differences in functional outcomes at 12 weeks after surgery.

Randomized clinical trials (RCTs) serve as the standard for clinical research and have contributed to major advances in patient care, yet they have several shortcomings. Adaptive trial design has been proposed as a means to increase the efficiency of RCTs, potentially benefiting trial participants and future patients while reducing costs and enhancing the likelihood of finding a true benefit of the therapy being studied. Adaptive trials apply to both exploratory trials aimed at finding a safe and efficient dose range and confirmatory trials aimed at testing the clinical benefit of a therapy/intervention. In this review, the authors focus on adaptive designs of confirmatory clinical trials and discuss the benefits and limitations of such designs, using four case studies that highlight the statistical and operational considerations for a successful trial. Readers will find here robust and easy-to-read information on how to identify patients who are most likely to derive benefit from a given therapy.

Take home message: Adaptive design applied to confirmatory clinical trials may help identify those patients who are most likely to derive benefit from a therapy.

Effect of a primary care management intervention on mental health–related quality of life among survivors of sepsis: A randomized clinical trial. JAMA 2016; 315:2703–11.

This randomized clinical trial examined if a primary care–based intervention improves mental health–related quality of life among survivors of sepsis. Two hundred ninety-one patients 18 yr or older who survived sepsis, including septic shock, were recruited from nine intensive care units (ICUs) across Germany. Participants were randomized to usual care (n = 143) or to a 12-month intervention (n = 148). Usual care was provided by their primary care physician (PCP) and included periodic contacts, referrals to specialists, and prescription of medication, other treatment, or both. The intervention included PCP and patient training, case management provided by trained nurses, and clinical decision support for PCPs by consulting physicians. The primary outcome was change in mental health–related quality of life between ICU discharge and 6 months after ICU discharge using the Mental Component Summary of the 36-Item Short-Form Health Survey. It was found that among survivors of sepsis and septic shock, the use of a primary care–focused team-based intervention, compared with usual care, did not improve mental health–related quality of life 6 months after ICU discharge.

Take home message: In this randomized controlled trial, a targeted, primary care intervention versus standard care did not improve mental health–related quality of life among sepsis survivors.

Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure. The objective of this single-center randomized clinical trial was to compare the effect of standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure on hospital length of stay (LOS; primary outcome). Patients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. Of the 300 randomized patients, the median hospital LOS was 10 days (interquartile range, 6 to 17) for the SRT group and 10 days (interquartile range, 7 to 16) for the usual care group (median difference, 0 [95% CI, –1.5 to 3], P = 0.41). No significant difference was observed between groups in most of the secondary outcomes (handgrip and dynamometer strength, 36-item Short-Form Health Surveys and Mini-Mental State Evaluation Score performed at 2, 4, and 6 months).

Take home message: Among patients hospitalized with acute respiratory failure, standardized rehabilitation therapy compared with usual care did not decrease hospital length of stay.

Rates of opioid addiction and deaths related to abuse have risen in parallel to liberalized prescribing practices over the past 15 yr. Opioid maintenance therapy with buprenorphine or methadone represents an important treatment option, although adherence to therapy is often problematic. To address this issue, a 6-month implantable form of buprenorphine was tested against a conventional sublingual formulation of the drug. Using a randomized, active-control, 24-week, double-blind study design involving 177 patients, the investigators found that the implantable formulation was noninferior to sublingual buprenorphine, and slightly better at promoting opioid abstinence (85.7 vs. 71.9%; P = 0.03 at 24 weeks). An important limitation of the generalizability of the study is that the patient population was predominantly educated and employed, characteristics associated with high rates of treatment response. Nonetheless, this trial suggests that use of implantable buprenorphine in the treatment of opioid addiction is promising.

Take home message: This randomized controlled trial shows promising results for implantable buprenorphine in the treatment of opioid addiction.

Moral courage, willingness to do the right thing even when it is not in your personal best interest, such as reporting an error or speaking up to authority, is a desirable quality to develop in resident physicians. Can it be taught? Can it be measured? These authors developed and provide initial validation of a method that can be used to measure and potentially track the development of moral courage in the context of clinical care. Three hundred fifty-two interns and residents in medicine and surgical specialties at two academic medical centers completed the Moral Courage Scale for Physicians as part of a voluntary safety culture survey. The 12-question survey tool addresses the five aspects that define moral courage. Correlation to established measures of empathy assessed validity. Perhaps this simple survey tool could be used to track effectiveness of educational interventions in professionalism, a competency that is challenging to measure.

Take home message: The authors developed a 12-question survey tool to assess moral courage of residents such as reporting an error or speaking up to authority.